Related Experiment Video

Updated: Jan 13, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
05:36

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

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HSP90AA1 restrains clear cell renal cell carcinoma progression by promoting CADM1 expression and suppressing the

Wuping Yang1, Yifan Li2, Zhi Li3

  • 1Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yangwuping@zju.edu.cn.

Cell Death Discovery
|January 8, 2026
PubMed

Insights

Heat shock protein 90 alpha family class A member 1 (HSP90AA1) is downregulated in clear cell renal cell carcinoma (ccRCC). Overexpressing HSP90AA1 inhibits ccRCC proliferation and metastasis by regulating the FBXO7/CADM1/PI3K-AKT pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Heat shock protein 90 alpha family class A member 1 (HSP90AA1) is implicated in various cancers, but its role in clear cell renal cell carcinoma (ccRCC) is not well understood.
  • Understanding HSP90AA1's function in ccRCC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the expression pattern, clinical significance, and biological function of HSP90AA1 in ccRCC.
  • To elucidate the downstream regulatory mechanism of HSP90AA1 in ccRCC progression.

Main Methods:

  • Analysis of GEO and TCGA-KIRC databases for HSP90AA1 expression and clinical significance.
  • Immunohistochemistry and Western blot to validate HSP90AA1 expression in ccRCC tissues and cell lines.
  • In vitro (colony formation, EdU, TUNEL, migration, invasion assays) and in vivo (mouse orthotopic xenograft model) experiments to assess HSP90AA1's biological effects.
  • Co-immunoprecipitation (Co-IP) and RNA sequencing (RNA-seq) to explore downstream mechanisms.

Main Results:

  • HSP90AA1 was significantly downregulated in ccRCC, with reduced expression correlating with tumor metastasis.
  • Overexpression of HSP90AA1 inhibited ccRCC cell proliferation and metastasis.
  • HSP90AA1 interacted with F-box only protein 7 (FBXO7), increasing its expression. FBXO7 downregulation was linked to poor prognosis.
  • FBXO7 promoted cell adhesion molecule 1 (CADM1) expression and suppressed the PI3K-AKT pathway. HSP90AA1 overexpression's effects were partially reversed by FBXO7 knockdown, which downregulated CADM1 and activated PI3K-AKT.

Conclusions:

  • HSP90AA1 acts as a tumor suppressor in ccRCC, exhibiting low expression and inhibiting proliferation and metastasis.
  • The HSP90AA1/FBXO7 axis regulates ccRCC progression by modulating CADM1 expression and the PI3K-AKT signaling pathway.

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